Scientific and Technical Aerospace Reports Volume 39 April 6, 2001

20010025069 Cleveland Clinic Foundation, Cleveland, OH USA
Isolation of Genes From Chromosome Region Ip31 Involved in the Development of Breast Cancer Annual Report, 1 Sep.
1998-31 Aug. 1999
Cowell, John K.; Sep. 1999; 14p; In English
Contract(s)/Grant(s): DAMD17-1-98-8294
Report No.(s): AD-A384614; No Copyright; Avail: CASI; A03, Hardcopy; A01, Microfiche
Loss of heterozygosity (LOH) involving the p31 region of chromosome 1 has been reported as one of the most frequent
genetic changes in human breast cancer. LOH is generally considered a mechanism for exposing recessive mutations in genes
critical for tumorigenesis. We have begun creating a contiguous array of bacterial artificial chromosome (BAC) clones spanning
the minimum region in Ip31 defined by LOH studies. These clones will facilitate the search for genes from the region which can
be tested for mutations in breast tumors. One such gene, TTC4, has been identified, cloned and characterized. This gene contains
a tetratricopeptide repeat motif which has been implicated in protein-protein binding and one member of this extended family of
genes has been implicated in liver tumorigenesis.
DTIC
Genes; Genetics; Cancer
20010025070 Cleveland Clinic Foundation, Cleveland, OH USA
Targeted Therapy of Human Breast Cancer by 2-5A-Antisense Directed Against Telomerase RNA Annual Report, 1 Sep.
1998-31 Aug. 1999
Cowell, John K.; Sep. 1999; 10p; In English
Contract(s)/Grant(s): DAMD17-98-1-8295
Report No.(s): AD-A384610; No Copyright; Avail: CASI; A02, Hardcopy; A01, Microfiche
In most normal cells DNA is lost from the ends of the chromosomes (telomeres) at each cell cycle. In rapidly growing tumor
cells this eventually results in chromosome instability and cell death. to overcome this problem most cancer cells re-express the
telomerase enzyme which prevents telomere erosion. To establish whether expressing telomerase is essential to maintain the
malignant phenotype in these tumor cells, we have used an anti sense oligonucleotide approach targeting the RNA component
of the telomerase enzyme. The oligonucleotides used carry a 2-5A moiety which activates RNAseL to selectively destroy the target
RNA. Using this system we have shown that targeting telomerase causes rapid cell death in several different breast cancer cell
lines in vitro. This cell death is not seen when the cells are treated with control oligos carrying mismatches in the target sequence.
Cell death is due to apoptosis.
DTIC
Ribonucleic Acids; Cancer; Therapy
20010025071 Colorado Univ., Denver, CO USA
Signaling the ErbB Receptors in Breast Cancer: Regulation by Compartmentalization of Heterodimetric Receptor Complexes
Annual Report, 15 Sep. 1998-14 Sep. 1999
Bild, Andrea H.; Johnson, Gary; Oct. 1999; 10p; In English
Contract(s)/Grant(s): DAMD17-98-1-8297
Report No.(s): AD-A384607; No Copyright; Avail: CASI; A02, Hardcopy; A01, Microfiche
MEKK1 and MEKK4 play a role in the signal transduction pathways of breast cancer cell proliferation, survival, and apoptosis.
Treatment with cancer chemotherapeutics, cell stresses, or anoikis activates MEKK1, which stimulates caspase activity. Caspases
cleave MEKK1, and this cleavage product of MEKK1 causes apoptosis. I show that expression of the oncogene Akt blocks
MEKK1-induced death by 90%. MEKK1-induced caspase activity is strongly inhibited by the expression of Akt to levels below
basal. Caspases inhibition by Akt protects cells from cleavage of endogenous MEKK1 to its active form.
DTIC
Enzymes; Cancer; Apoptosis
20010025304 Wisconsin Univ., Madison, WI USA
Mechanisms Underlying the Very High Susceptibility of the Immature Mammary Gland to Carcinogenic Initiation Final
Report, 1 Jul. 1996-30 Jun. 00
Gould, Michael N.; Jul. 2000; 44p; In English
Contract(s)/Grant(s): DAMD17-96-1-6028
Report No.(s): AD-A385875; No Copyright; Avail: CASI; A03, Hardcopy; A01, Microfiche
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